POS1400 CLINICAL EVIDENCE OF THE DIFFERENCE IN CIRCULATING CALPROTECTIN LEVELS BETWEEN RHEUMATOID ARTHRITIS AND HEALTHY INDIVIDUALS, NON-INFLAMMATORY ARTHRITIS OR OTHER INFLAMMATORY ARTHRITIS: A SYSTEMATIC LITERATURE REVIEW AND META-ANALYSIS
Authors: C. Andalucia, R. Albesa, M. Mahler
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) is a systemic autoimmune disease mainly characterized by a chronic inflammation of the joints. Early diagnosis and treatment with disease-modifying antirheumatic drugs (DMARDs) is essential to prevent or slow down the structural damage. Diagnosis might be difficult in patients with mild and unspecific clinical signs and symptoms though. A differential diagnosis in patients presenting arthritis is needed for an appropriate patient management. Acute-phase reactants (ESR or CRP) are non-specific inflammatory biomarkers used to aid in the diagnosis of RA and to assess disease activity. In the recent years, studies published have shown that calprotectin may be an alternative biomarker of active inflammatory disorders as well as a prognostic or monitoring biomarker. Objectives To collect all available evidence on the difference between circulating calprotectin (cCalpro) levels in rheumatoid arthritis (RA) patients and other control populations such as healthy individuals (HI), osteoarthritis (OA), psoriatic arthritis (PsA) or spondyloarthritis (SpA). Methods Electronic databases searches (Scopus, Pubmed and Cochrane Library), complemented by registry and hand searching, were conducted (February 4 th , 2021) to identify fully paired studies comparing cCalpro levels in RA and HI, non-inflammatory arthritis (NIA), or other inflammatory arthritis. As recommended by Cochrane, the Hedge´s standardized mean difference (SMD) and its 95% confidence intervals were used to synthetize the difference in cCalpro levels from studies using different matrices (serum or plasma) or laboratory methods. Sample size, mean and standard deviation of each group were extracted from the individual studies to conduct a random-effects model meta-analysis in STATA MP v17.0. When cCalpro levels were reported in median and range or inter-quartile, a formula was used to estimate the mean and standard deviation. Sensitivity analysis, subgroup analyses and meta-regression analyses on matrix type (serum or plasma) and cCalpro commercial test were performed, when feasible, to investigate heterogeneity. Results The systematic review retrieved 27 studies comparing cCalpro levels between RA and controls. One study reported cCalpro levels in three different RA and HI cohorts. Most of RA and controls were age and gender matched. Calprotectin was measured in serum in 72,4% of the comparisons. Thirteen different commercial calprotectin tests and four homemade tests were used. In 21 studies cCalpro levels were measured in 2678 RA and 1096 HI. cCalpro levels were significantly higher in RA than in HI (SMD=2,13;95%CI=1,27-2,98;p&lt;0,0001), and significant heterogeneity was observed. A meta-regression on matrix and assay manufacturer indicated that 22% of the between-study variance might be explained by the type of calprotectin test used. Five studies compared cCalpro levels in 207 RA and 187 NIA (78,57% OA). cCalpro levels were significantly higher in RA than in NIA (SMD=2,914;95% CI=0,957-4,872;p=0,0035), significant heterogeneity was observed. cCalpro levels in 1217 RA and 411 PsA patients were reported in 5 studies. cCalpro levels were slightly higher in RA than in PsA (SMD=0,54; 95%CI=0,424-0,656; p&lt;0,0001), while no significant heterogeneity was observed. A comparison between cCalpro levels in RA and SpA was included in 4 studies. cCalpro levels were slightly higher in RA than in SpA (SMD=0,35; 95%CI=0,129-0,576; p=0,0020), and no significant heterogeneity was observed. Conclusion In this systematic review and meta-analysis, rheumatoid arthritis patients showed significantly higher circulating calprotectin levels than healthy individuals, non-inflammatory arthritis, psoriatic arthritis and spondyloarthritis. Pooled standardized mean difference between groups should be interpretated with cautious due to substantial heterogeneity or small number of studies. Disclosure of Interests Carmen Andalucia Employee of: Werfen, Roger Albesa Employee of: Werfen, Michael Mahler Employee of: Werfen